Glomerular diseases (primary glomerular nephritis), which develop in glomeruli of the kidneys, are clinically classified into seven types; i.e., acute nephritis after infection with hemolytic streptococcus, crescentic glomerulonephritis (rapidly progressive glomerulo nephritis), IgA nephropathy, membranous nephropathy, membranous proliferative nephropathy, focal glomerulonephritis, and minimal change nephrotic syndrome. Of these, the diseases other than acute nephritis after infection with hemolytic streptococcus, crescentic of glomerulonephritis, and minimal change nephrotic syndrome are generally called “chronic glomerular nephritis,” but it remains to be elucidated about the cause and time of the onset of chronic glomerular nephritis. In the lesion processes chronic glomerular nephritis, most of them are generally progressive, and often result in renal failure.
In many cases, chronic glomerular nephritis is often recognized by a lesion occurring in glomeruli. The lesion is thought to largely associate with proliferation of mensagial cells (i.e., a type of constituent cells of a glomerulus) and an increase in the amount of the mensagial matrix (i.e., the extra-mensagial-cellular matrix). Recent studies have suggested that cytokines/growth factors, such as PDGF-BB and TGF-β1, play an active role in causing a lesion in the mesangium (i.e., mesangial cells and the mesangial matrix). For example, PDGF-BB, which is produced from mesangial cells, is known to promote proliferation of the mesangial cells (Yoshimura A. et al, Kidney int., 40:470, 1991), and TGF-β1 is known to promote synthesis and secretion of the mesangial matrix (Border W A. et al, Nature., 346:371, 1990).
Therefore, suppressing the response of mesangial cells to PDGF-BB or TGF-β1 and inhibiting proliferation of mesangial cells and hyperplasia of the mensagial matrix are considered to be able to arrest the progress of a lesion occurring in the mensangium, and further to arrest the progress of a glomerular disease. Thus, a variety of such drugs (e.g., a mesangial cell proliferation inhibitor) have heretofore been investigated according to the pathological model (Fitner F. et al, Kidney int., 51(1)69, 1997).
However, an effective therapeutic agent for a glomerular disease has not been developed to date, and therefore, strong demand exists for the development of a novel drug exerting an excellent therapeutic effect on patients suffering from the aforementioned glomerular diseases.
Thus, an object of the present invention is to provide a preventive or therapeutic agent for a glomerular disease involving a lesion occurring in a glomerulus, particularly caused by a lesion in the mesangium.